Drug Discovery

Neuroprotection

A Novel Drug Target in Alzheimer’s Disease

Investigator(s): Marcos Marques, PhD

Institution(s): ApoLogic, Inc, Cincinnati Ohio

Duration: 2002 - 2004

Summary:

Apolipoprotein E (ApoE) is an important genetic risk factor for late onset Alzheimer’s disease (AD) suggesting that it is a relevant target for AD therapy. Scientists at ApoLogic recently discovered that proteolytic cleavage of ApoE produces neurotoxic fragments. Data suggest that the risk enhancing activity of ApoE may stem, in part, from its neurotoxic (nerve cell killing) activity. ApoLogic has developed a therapeutic strategy to discover compounds that inhibit ApoE cleavage and reduce the levels of neurotoxic fragments. In this program ApoLogic will screen a large panel of commercially available protease inhibitors for their ability to inhibit the formation of ApoE neurotoxic fragments. This will identify the most effective chemical class of inhibitors. Subsequently, scientists at ApoLogic will screen large chemical libraries related to inhibitors found in the initial studies to generate novel lead compounds. Although a clear risk factor, there are few programs targeting ApoE for drug discovery in AD. This program is a novel approach to the development of ApoE therapeutics.